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Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block.

Publication ,  Journal Article
Yi, G; Grill, WM
Published in: PLoS computational biology
June 2020

The delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimization approach to design blocking waveforms that eliminated the onset response by moving voltage-gated Na+ channels (VGSCs) to closed-state inactivation (CSI) without first opening. We used computational models and particle swarm optimization (PSO) to design a charge-balanced 10 kHz biphasic current waveform that produced conduction block without onset firing in peripheral axons at specific locations and with specific diameters. The results indicate that it is possible to achieve onset-free KHFAC nerve block by causing CSI of VGSCs. Our novel approach for designing blocking waveforms and the resulting waveform may have utility in clinical applications of conduction block of peripheral nerve hyperactivity, for example in pain and spasticity.

Duke Scholars

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Published In

PLoS computational biology

DOI

EISSN

1553-7358

ISSN

1553-734X

Publication Date

June 2020

Volume

16

Issue

6

Start / End Page

e1007766

Related Subject Headings

  • Voltage-Gated Sodium Channels
  • Ranvier's Nodes
  • Peripheral Nerves
  • Neural Conduction
  • Nerve Block
  • Models, Neurological
  • Markov Chains
  • Ions
  • Humans
  • Electrodes
 

Citation

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Yi, G., & Grill, W. M. (2020). Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block. PLoS Computational Biology, 16(6), e1007766. https://doi.org/10.1371/journal.pcbi.1007766
Yi, Guosheng, and Warren M. Grill. “Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block.PLoS Computational Biology 16, no. 6 (June 2020): e1007766. https://doi.org/10.1371/journal.pcbi.1007766.
Yi, Guosheng, and Warren M. Grill. “Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block.PLoS Computational Biology, vol. 16, no. 6, June 2020, p. e1007766. Epmc, doi:10.1371/journal.pcbi.1007766.

Published In

PLoS computational biology

DOI

EISSN

1553-7358

ISSN

1553-734X

Publication Date

June 2020

Volume

16

Issue

6

Start / End Page

e1007766

Related Subject Headings

  • Voltage-Gated Sodium Channels
  • Ranvier's Nodes
  • Peripheral Nerves
  • Neural Conduction
  • Nerve Block
  • Models, Neurological
  • Markov Chains
  • Ions
  • Humans
  • Electrodes